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| Status |
Public on Oct 11, 2020 |
| Title |
Cytoplasmic Miz1 Suppresses TNF-α-Induced NF-κB Activation and Hepatocellular Carcinoma Progression via the Interaction with Metadherin |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Previous studies have revealed that nuclear Miz1 is implicated in the regulation of several cancers mainly relying on its POZ domain. Current study, however, uncovers an unexpected function of cytoplasmic Miz1 in hepatocellular carcinoma (HCC). In vivo HCC models in Miz1 and Miz1(POZ) KO mice along with RNA-sequencing experiments show that hepatocyte specific ablation of Miz1 exacerbates TNF-α-induced NF-κB activation and promotes the progression of HCC independent of its transcriptional activity. Ubiquitination and proteosomal degradation of cytoplasmic Miz1 liberates its novel partner Metadherin (MTDH), and its site specific phosphorylation is critical to NF-κB activation. These findings reveal a brand new role of cytosolic Miz1 as a suppressor of HCC, and provide profound insights into liver cancer diagnosis and treatment.
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| Overall design |
Miz1fl/fl and Miz1(POZ)fl/fl mice were crossed with Alb-Cre transgenic mice (C57BL/6 background) to generate an hepatocyte specific knock out of Miz1 and Miz1(POZ) respectively(Miz1△Hep, Miz1(POZ)△Hep). For different groups of mice (Miz1fl/fl, Miz1△Hep, Miz1(POZ)fl/fl, Miz1(POZ)△Hep), HCC was induced by the combination of DEN (25 mg/kg i.p.) given at Week 2 postpartum followed by weekly injections of CCl4 (0.5 ml/kg i.p., dissolved in corn oil). Mice were sacrificed at the age of 5 months and pure tumors from Miz1fl/fl, Miz1△Hep, Miz1(POZ)fl/fl, Miz1(POZ)△Hep mice were subjected to RNA sequencing, in triplicate. All animal experimental protocols were approved by the Animal Ethics Committee of Nanjing Medical University.
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| Contributor(s) |
Zhang W, Zhangyuan G, Jin K, Wang F, Wang X, Yu W, Huang R, Xu X, Shen H, Du M, Zhang H, Yin Y, Zhong G, Lin A, Sun B |
| Citation missing |
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| Submission date |
Oct 13, 2017 |
| Last update date |
Oct 11, 2020 |
| Contact name |
Guangyan Zhangyuan |
| E-mail(s) |
zygy1992@163.com
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| Phone |
86-025-86560946
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| Organization name |
Nanjing University
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| Department |
Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School
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| Street address |
321 Zhongshan Road
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| City |
Nanjing |
| State/province |
Jiangsu |
| ZIP/Postal code |
210000 |
| Country |
China |
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| Platforms (2) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA414205 |
| SRA |
SRP119908 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE104940_Miz1.xls.gz |
1.3 Mb |
(ftp)(http) |
XLS |
| GSE104940_Miz1_POZ_.xls.gz |
843.9 Kb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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